Caffeine is widely consumed. Previous work from our laboratory shows that caffeine can provoke anxiety and even panic attacks in susceptible persons. However, caffeine physical dependence and withdrawal effects have been incompletely characterized in humans. A number of anecdotal reports suggest certain symptoms, but no systematic study has been made of the effects of caffeine withdrawal in anxiety patients, depressed patients, or normal volunteers. The neurochemical mechanisms underlying the caffeine abstinence syndrome are poorly understood. This exploratory study investigates the clinical and biochemical correlates of caffeine withdrawal in normal controls, affectively ill patients, and anxiety disorder patients.